Leishmaniasis is a major and severe parasitic disease of humans, canids (dogs, wolves, foxes, coyotes, jackals), and felids (lions, tigers, domestic cats, wild cats, other big cats, and other felines including cheetahs and lynx).
The agent of leishmaniasis is a protozoan parasite and belongs to the leishmania donovani complex. This parasite is widely distributed in temperate and subtropical countries of Southern Europe, Africa, Asia, South America and Central America (Desjeux P., Trans. R. Soc. Trop. Med. Hyg., 2001, 95: 239-43). Leishmania donovani infantum (L. infantum) is responsible for the feline and canine disease in Southern Europe, Africa, and Asia. In South America and Central America, the agent is Leishmania donovani chagasi (L. chagasi), which is closely related to L. infantum. In humans, the agent is Leishmania donovani donovani (L. donovani), which is closely related to L. infantum and L. chagasi. 
The parasite is transmitted to humans, felids and canids by sand flies, which species vary depending on the geographic location. Phlebotomus ariasi (P. ariasi) and Phlebotomus perniciosus (P. perniciosus) are the carriers most common in Southern Europe, Africa, and Asia, whereas Lutzomyia longipalpis (L. longipalpis) is most common in Southern and Central America.
The domestic reservoir of Leishmaniasis are dogs, which may suffer from a severe disease characterized by chronic evolution of viscero-cutaneous signs occurring in less than 50% of infected animals (Lanotte G. et al., Ann. Parasitol. Hum. Comp., 1979, 54: 277-95). On the other hand, both asymptomatic and symptomatic dogs with detectable antibodies can be infectious to phlebotomine vectors (Molina R. et al., Trans. R. Soc. Trop. Med. Hyg., 1994, 88: 491-3; Courtenay O. et al., J. Infect. Dis., 2002, 186: 1314-20). Cats can be carriers of the protozoan parasites and are considered as secondary potential reservoirs.
These parasites cause visceral leishmaniasis and/or cutaneous leishmaniasis. Visceral leishmaniasis results in clinical symptoms like fever, cachexia, hepatosplenomegaly (enlargement of the liver and spleen), and blood cytopenia. Cutaneous leishmaniasis occurs in varying presentations, from the self-limited and even self-healing cutaneous forms to fatal systemic disease. Lesions of cutaneous leishmaniasis may occur anywhere on the body but the most common sites are those which are exposed to the environment and are therefore more susceptible to bites from the sand flies. The initial papule rapidly gives rise to an ulcer. Systemic leishmaniasis is rare but is invariably fatal if not treated promptly. Systemic leishmaniasis affects the internal body organs, specifically the spleen and the liver.
In canines, the disease is associated with cutaneous symptoms or with visceral symptoms or both cutaneous and visceral symptoms, and is lethal in the absence of therapy.
Numerous treatments have been described but none is fully satisfactory due to toxicity of the treatment itself or a tendancy for the animal to relapse.
Mass detection of seropositive dogs followed by culling and/or drug treatment, or the mass application of deltamethrin-impregnated collars, was shown to have an impact in reducing human and canine Leishmaniasis prevalence in endemic areas of Southern Europe, Africa, and Asia (Maroli M. et al., Med. Vet. Entomol., 2001, 15: 358-63; Mazloumi Gavgani A. S. et al., Lancet, 2002, 360: 374-9), although the efficacy of eliminating seropositive canines has been debated (Dietze R. et al., Clin. Infect. Dis., 1997, 25: 1240-2; Moreira Jr. E. D. et al., Vet. Parasitol., 2004, 122: 245-52). These control measures are either considuer unacceptable, expensive or not effective (Gradoni L. et al., Vaccine, 2005, 23: 5245-51).
Mathematical models used to compare the effectiveness of various tools for controlling Leishmaniasis suggest that a canine vaccine may be the most practical and effective method (Dye C., Am. J. Trop. Med. Hyg., 1996, 55: 125-30). Therefore, the development of vaccines able to protect canids from leishmaniasis and/or to prevent disease progression in infected animals, is highly desirable for the implementation of Leishmaniasis control programs as well for the veterinary community (Gradoni L. et al., Vaccine, 2005, 23: 5245-51).
The state of the art is best summarized in US patent application US-A-2006/0194753. This document describes a vaccine containing a DNA expression vector encoding L. infantum KMP11 (kinetoplastid membrane protein 11) protein. However, the experimental results on mice (as shown in FIG. 1 of 2006/0194753) showed that mice vaccinated with pMCV1.4 plasmids expressing KMP11 had worse results than the control mice as to the presence of lesions within 8 weeks after challenge infection (lesion scores of about 3.2 and about 1.6 for vaccinated and control mice, respectively). Furthermore, experiments on dogs in FIG. 2 of 2006/0194753 show that after administration of a mixture of one recombinant pMOK plasmid expressing L. infantum p36 antigen and three recombinant pMCV1.4 plasmids expressing L. infantum TSA (thiol-specific antioxidant protein), L. infantum gp63 and L. infantum KMP11 antigens, no antibodies were detectable. There was no clear difference between the results of the vaccinated group and those of the control group. After challenge infection with 107.7 L. infantum promastigotes, the number of infected dogs in the vaccinated group showed only a slight difference to the control group.
Basu et al. (Basu R. et al., J. Immunol., 2005, 174: 7160-71) described an experiment using golden hamsters immunized with KMP11 containing pCMV-LIC mammalian expression vector versus control animals immunized with a blank vector construct not harboring KMP11 (pCMV-LIC). Animals of both groups received two intramuscular administrations to the hind leg thigh muscle (using a 28-guage needle), given 8 days apart, of 100 μg of plasmids dissolved in saline. On day 15, a lethal parasite challenge was done with either of two strains, L donovani AG83 or L. donovani GE1F8R. All of the vaccinated hamsters immunized with KMP11 DNA survived the lethal challenge of AG83 and GE1F8R and remained healthy until the termination of the experiment at 8 months postinfection, whereas all non-immunized and blank vector-immunized hamsters succumbed to virulent L. donovani challenge within 6 months.
Currently, no vaccine is available for Leishmania-susceptible subjects, including for canids.